An intraoperative evaluation of the cerebral circulation using the ophthalmic artery Doppler method in a case of brachiocephalic trunk occlusion

A 57-year-old man underwent left-right subclavian artery bypass for brachiocephalic trunk occlusion. The cerebral circulation was evaluated by ophthalmic artery Doppler method during the operation. Before the bypass, maximal flow velocity (Vmax) of the right ophthalmic artery was 6.09 cm x sec(-1), compared to 43.8 cm x sec(-1) of the left. The preoperative flow acceleration (FA) was 8.3 cm x sec(-2) and 500 cm x sec(-2) in the right and left, respectively. Both Vmax and FA of the right ophthalmic artery improved to 17.6 cm x sec(-1) and 96.7 cm x sec(-2) at the end of the bypass. Additional sutures were performed because of difficulty in stopping bleeding at the site of anastomosis. However, this additional procedure blunted the Doppler waveform, with decreases in Vmax to 8.69 cm x sec(-1) and FA to 33.1 cm x sec(-2) Re-anastomosis at the leftsubclavian artery was performed. Anaphylactic shock induced by transfusion was encountered at the end of re-bypass. Vmax of the right ophthalmic artery at that time was only 10.2 cm x sec(-1) However, the fact, that the Doppler waveform was no more blunt and FA had improved up to 116.4 cm x sec(-2), let us conclude that the cerebral circulation had recovered. In conclusion, the ophthalmic artery Doppler method is a useful tool for evaluation of the cerebral circulation.     

New molecular mechanisms for cardiovascular disease:blood flow sensing mechanism in vascular endothelial cells

Endothelial cells (ECs) lining blood vessels have a variety of functions and play a critical role in the homeostasis of the circulatory system. It has become clear that biomechanical forces generated by blood flow regulate EC functions. ECs are in direct contact with blood flow and exposed to shear stress, a frictional force generated by flowing blood. A number of recent studies have revealed that ECs recognize changes in shear stress and transmit signals to the interior of the cell, which leads to cell responses that involve changes in cell morphology, cell function, and gene expression. These EC responses to shear stress are thought to play important roles in blood flow-dependent phenomena such as vascular tone control, angiogenesis, vascular remodeling, and atherogenesis. Much research has been done on shear stress sensing and signal transduction, and their molecular mechanisms are gradually becoming understood. However, much remains uncertain, and many candidates have been proposed for shear stress sensors. More extensive studies of vascular mechanobiology should increase our understanding of the molecular basis of the blood flow-mediated control of vascular functions.     

Serum vitamin C concentration and hs-CRP level in middle-aged Japanese men and women

ObjectiveTo examine the association between concentrations of serum vitamin C, a contributive factor to prevention of cardiovascular disease and levels of hs-CRP, a risk factor for cardiovascular disease, in population-based samples of middle-aged men and women.DesignA cross-sectional study.Methods and resultsThe subjects were 778 men and 1404 women, aged 40–69 years, who participated in a cardiovascular risk survey in Kyowa, Ibaraki prefecture in 2002 as part of the Circulatory Risk in Communities Study (CIRCS). Inverse associations between serum vitamin C concentrations and hs-CRP levels were established for both men and women. Multivariable-adjusted mean values of hs-CRP for the lowest to highest quintiles of vitamin C levels were 0.75, 0.65, 0.61, 0.61 and 0.47 mg/L (P for trend <0.001) for men, and 0.56, 0.51, 0.49, 0.41 and 0.41 mg/L (P for trend <0.001) for women. The inverse association between vitamin C and hs-CRP was stronger for non-smoking men and women, non-overweight women and postmenopausal women.ConclusionsSerum vitamin C concentrations were found to be inversely associated with hs-CRP levels in both men and women, primarily among non-smokers, non-overweight women and postmenopausal women. The respective roles of serum vitamin C and hs-CRP levels in the development of cardiovascular disease thus warrant further investigation.     

Fibronectin/integrin system is involved in P2X(4) receptor upregulation in the spinal cord and neuropathic pain after nerve injury

We have previously shown that activation of the ATP-gated ion channel subtype P2X(4) receptors (P2X(4)Rs) in the spinal cord, the expression of which is upregulated in microglia after nerve injury, is necessary for producing neuropathic pain. The upregulation of P2X(4)Rs in microglia is, therefore, a key process in neuropathic pain, but the mechanism remains unknown. Here, we find a fibronectin/integrin-dependent mechanism in the upregulation of P2X(4)Rs. Microglia cultured on dishes coated with fibronectin, an extracellular matrix molecule, expressed a higher level of P2X(4)R protein when compared with those cultured on control dishes. The increase was suppressed by echistatin, a peptide that selectively blocks beta(1) and beta(3)-containing integrins, and with a function-blocking antibody of beta(1) integrin. In in vivo studies, the upregulation of P2X(4)Rs in the spinal cord after spinal nerve injury was significantly suppressed by intrathecal administration of echistatin. Tactile allodynia in response to nerve injury and intrathecal administration of ATP- and fibronectin-stimulated microglia was inhibited by echistatin. Furthermore, intrathecal administration of fibronectin in normal rats increased the level of P2X(4)R protein in the spinal cord and produced tactile allodynia. Moreover, the fibronectin-induced allodynia was not observed in mice lacking P2X(4)R. Taken together with the results of our previous study showing an increase in the spinal fibronectin level after nerve injury, the present results suggest that the fibronectin/integrin system participates in the upregulation of P2X(4)R expression after nerve injury and subsequent neuropathic pain.     

Uniformity and Efficacy of Dry Powders Delivered to the Lungs of a Mycobacterial-Surrogate Rat Model of Tuberculosis

Pharmaceutical Research - Pulmonary administration of dry drug powder is a considered promising strategy in the treatment of various lung diseases such as tuberculosis and is more effective than...     

Temporal lobe epilepsy associated with hippocampal sclerosis and a contralateral middle fossa arachnoid cyst.

We report on a 13-year-old boy with temporal lobe epilepsy associated with left hippocampal sclerosis and a contralateral arachnoid cyst in the middle cranial fossa (ACMCF). Chronic intracranial recording from subdural grid electrodes showed the left medial temporal lobe to be the ictal onset zone. After left anterior temporal lobectomy with hippocampectomy, seizure control was improved. ACMCF was not considered the direct cause of epilepsy; instead the seizures were attributed to hippocampal sclerosis.     

Progressive hair loss and myocardial degeneration in rough coat mice: reduced lysyl oxidase-like (LOXL) in the skin and heart

The rough coat (rc) is a spontaneous recessive mutation in mice. To identify the mutated gene, we have characterized the rc phenotype and initiated linkage mapping. The rc mice show growth retardation, cyclic and progressive hair loss, hyperplastic epidermis, abnormal hair follicles, cardiac muscle degeneration, and reduced amount of collagen and elastin in the skin and heart. The rc locus was mapped at 32.0 cM on chromosome 9, close to the loxl gene. Lysyl oxidase-like (LOXL) protein is a novel copper-containing amine oxidase that is required for the cross-linking of elastin and collagen in vitro. LOXL is expressed at high levels in the skin and heart, where the rc mice show strong phenotype. The expression pattern and the genetic proximity to rc suggested loxl as a potential candidate gene. In rc mice, the loxl mRNA was reduced in the skin and the LOXL protein in the heart, dermis, atrophic hair follicles, and sebaceous glands. No mutations, however, were identified within the coding region of loxl, and offspring from rc/rc and loxl null mice crossing were phenotypically normal. Based on these results, loxl appears non-allelic to rc. Heart- and skin-specific downregulation of LOXL in rc mice, however, may contribute to the extracellular matrix alterations and the rc phenotype.     

Impaired astrocytes and diffuse activation of microglia in the cerebral cortex in simian immunodeficiency virus-infected Macaques without simian immunodeficiency virus encephalitis

Various types of neuronal damage have been reported in acquired immunodeficiency syndrome (AIDS) dementia. We previously demonstrated that inflammation and cortical damage occur independently according to viral tropism in a simian immunodeficiency virus (SIV)-infected macaque model of AIDS dementia. To elucidate the pathogenesis of cortical degeneration, we examined the frontal cortex of SIV-infected macaques and found apoptosis and decreased expression of the excitatory amino acid transporter 2 in astrocytes and diffuse activation of microglia in association with limited neuronal damage. Some activated microglia also expressed excitatory amino acid transporter 2 but not proinflammatory cytokines. No inflammatory changes were seen in the cortex or the white matter, and SIV-infected cells were not detected in or around cortical lesions either by immunohistochemistry or by the polymerase chain reaction detection of SIV genomes of extracted DNA from microdissected tissue samples. These results indicate that an astrocytic abnormality and a compensatory activation of microglia might provide a protective effect against neuronal degeneration in the frontal cortex of SIV-infected macaques without SIV encephalitis.     

Comparative study of the distribution of the alpha-subunits of voltage-gated sodium channels in normal and axotomized rat dorsal root ganglion neurons

We compared the distribution of the α‐subunit mRNAs of voltage‐gated sodium channels Nav1.1–1.3 and Nav1.6–1.9 and a related channel, Nax, in histochemically identified neuronal subpopulations of the rat dorsal root ganglia (DRG). In the naïve DRG, the expression of Nav1.1 and Nav1.6 was restricted to A‐fiber neurons, and they were preferentially expressed by TrkC neurons, suggesting that proprioceptive neurons possess these channels. Nav1.7, ‐1.8, and ‐1.9 mRNAs were more abundant in C‐fiber neurons compared with A‐fiber ones. Nax was evenly expressed in both populations. Although Nav1.8 and ‐1.9 were preferentially expressed by TrkA neurons, other α‐subunits were expressed independently of TrkA expression. Actually, all IB4⁺ neurons expressed both Nav1.8 and ‐1.9, and relatively limited subpopulations of IB4⁺ neurons (3% and 12%, respectively) expressed Nav1.1 and/or Nav1.6. These findings provide useful information in interpreting the electrophysiological characteristics of some neuronal subpopulations of naïve DRG. After L5 spinal nerve ligation, Nav1.3 mRNA was up‐regulated mainly in A‐fiber neurons in the ipsilateral L5 DRG. Although previous studies demonstrated that nerve growth factor (NGF) and glial cell‐derived neurotrophic factor (GDNF) reversed this up‐regulation, the Nav1.3 induction was independent of either TrkA or GFRα1 expression, suggesting that the induction of Nav1.3 may be one of the common responses of axotomized DRG neurons without a direct relationship to NGF/GDNF supply. J. Comp. Neurol. 510:188–206, 2008. © 2008 Wiley‐Liss, Inc.